A large part of the medial temporal lobe consists of the hippocampal formations. Neuropathologic and clinical studies place atrophy in the hippocampal formations central in the processes related to the development of Alzheimer's disease (AD). Neuropathologic studies show that the hippocampal formations are among the first to be diseased by the two classic lesions in AD, neuritic plaques and tangles. The hippocampal formations are also involved in short and long term memory, disturbances in which are one of the sentinel cognitive signs of AD. Hippocampus formations have also been shown to be smaller in persons with AD compared to controls. This evidence has led to the proposal that hippocampal atrophy be used as an aid to the diagnosis of AD and a predictor of future AD. Because there is evidence from several different types of studies that the hippocampus plays a central role in the AD, examining risk factors for hippocampal atrophy may help to gain insight into the etiology of AD. As a putative intermediate step in the dementing process, research on risk factors for hippocampal atrophy may help to formulate possible interventions in the early stages of AD. To date studies of risk factors for hippocampal atrophy are limited to small studies of socio-economic correlates. In 2001 we collaborated with Dr. MMB Breteler to examine factors associated with hippocampal atrophy in the Rotterdam Scan Study. This project is now finished. However, we continue to make use of data from the Honolulu -Asia Aging Study to examine the association of mid-life risk factors with hippocampal volumes. As a part of the HAAS cohort, 575 men underwent magnetic resonance imaging (MRI) in 1994-1996. All hippocampal volumes and intracranial volume were measured by one person. Manuscripts are currently in preparation. This year we have extended our ability to study risk factors by collaborating with the Laboratory for Neuroimaging, UCLA in a project to look at hippocampal shape and risk factors